Chemokine Receptor Antagonist Lowers Intraocular Pressure and Prevents Retinal Degeneration in an Animal Model Glaucoma

Abstract

Purpose: : To investigate the in vivo effects of antagonism of the chemokine receptor CXCR3 in a rat model of glaucoma.

Methods: : Long-Evans male rats underwent episcleral vein cauterization in order to induce stable elevation in intraocular pressure (IOP). CXCR3 antagonist or the vehicle only were injected in glaucomatous eyes (n=10 in each), which were assessed for IOP weekly. Measurement of the trabecular filtrating function (fluorophotometry, dynamic recording of fluid turn-over, and microsphere injection combined with confocal microscopy of the trabecular meshwork), retinal nerve fiber count by scanning laser ophthalmoscopy, and optokinetic testing to assess visual function were conducted two months after.

Results: : IOP was significantly decreased during at least 6 weeks in glaucoma eyes treated with the antagonist compared to eyes receiving the vehicle only (P<0.01 at each time point). Aqueous humor outflow was increased in treated eyes (P<0.01) due to an increase in trabecular filtrating surface (P<0.01). Retinal nerve fiber density was higher in treated eyes than in untreated eyes (P<0.01), and further correlated with the visual function (P<0.01).

Conclusions: : In vivo blockade of the chemokine receptor CXCR3 in a rat model of glaucoma lowers ocular hypertension by restoring trabecular function and protects the retina against IOP-related degeneration. These original findings open new therapeutic avenues based on chemokine/chemokine receptor targeting in glaucoma.

Keywords: cytokines/chemokines • apoptosis/cell death • trabecular meshwork